Rifamycins, which are a group of macrocylic hydroquinonequinone antibiotics having a close relationship to each other, are described in Antibiotics Annual, 262 (1959), Appl. Microbiol., 9, 325 (1961), and Progr. Ind. Microbiol, 6, 21 (1967).
Rifamycin derivatives have been prepared by the chemical conversion of rifamycin B, which is an antibiotic produced by fermenting Nocardia mediterranei. Among these, rifamycin O and rifamycin S, the key intermediates for the synthesis of rifamycin derivatives are of great therapeutic use and, have been prepared from rifamycin B by chemical processes. Many efforts have been made for the improvement of this process, as can be seen from prior art such as the description of Japan Kokai No. 37-8,550, Japan Kokai 38-15,352, British Pat. No. 324,452, and German Pat. No. 2,444,527. Recovery of rifamycins from the fermentation broth has also been disclosed in many reports. Two kinds of recovery processes are known: as rifamycin B, in Progr. Ind. Microbiol., 6,21 (1967); and as rifamycin O, in U.S. Pat. No. 3,847,903, French Patent No. 2,221,517, Netherlands Pat. No. 73-03,196, Japan Kokai No. 49-117,692, German Pat. No. 2,310,731, and South African Pat. No. 73-01,328. The recovery of rifamycin O is essentially based on the chemical oxidation of rifamycin B.
In general, the oxidation of rifamycin B to rifamycin O is carried out in an organic solvent or an organic solvent-water mixture. Artificial oxidants such as sodium nitrite, sodium persulfate or hydrogen peroxide are usually employed at a slightly acidic condition (pH 4.5). The hydrolysis of rifamycin O to rifamycin S also spontaneously occurs at a more acidic condition. The improved processes for the preparation of rifamycin S from rifamycin O are disclosed in British Pat. No. 924,472 and German Pat. No. 2,444,527. All the processes hitherto reported are essentially based on chemical processes which require artificial oxidants and a strong acidic condition, where the substantial formation of by-products cannot be obviated. Therefore, an enzymatic process is desirable, in which the conversion can be carried out with a quantitative yield due to the mild condition employed and the specificity of the enzyme.